Details of the Drug Combination

General Information of Drug Combination (ID: DCG0IRQ)

Drug Combination Name
Ambrisentan Tadalafil
Indication
Disease Entry Status REF
Pulmonary arterial hypertension Phase 1 [1]
Component Drugs Ambrisentan   DMD1QXW Tadalafil   DMJZHT1
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ambrisentan
Disease Entry ICD 11 Status REF
Pulmonary arterial hypertension BB01.0 Approved [2]
Ambrisentan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Endothelin A receptor (EDNRA) TTKRD0G EDNRA_HUMAN Antagonist [5]
------------------------------------------------------------------------------------
Ambrisentan Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
------------------------------------------------------------------------------------
Ambrisentan Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [7]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [7]
------------------------------------------------------------------------------------
Indication(s) of Tadalafil
Disease Entry ICD 11 Status REF
Benign prostatic hyperplasia GA90 Approved [3]
Erectile dysfunction HA01.1 Approved [4]
Plasma cell myeloma 2A83.1 Approved [3]
Pulmonary hypertension BB01 Approved [3]
Priapism N.A. Investigative [3]
Tadalafil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phosphodiesterase 5A (PDE5A) TTJ0IQB PDE5A_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Tadalafil Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
------------------------------------------------------------------------------------
Tadalafil Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Tadalafil Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A) OTT8Q1AP PDE5A_HUMAN Decreases Activity [11]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hypertension, Pulmonary DCRZVRG N. A. Phase 1 [12]
------------------------------------------------------------------------------------

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3951).
3 Tadalafil FDA Label
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7299).
5 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
6 Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther. 2010 Oct;88(4):513-20.
7 Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805.
8 Pulmonary arterial hypertension: the most devastating vascular complication of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii25-31.
9 In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil. Biol Pharm Bull. 2017;40(8):1314-1319.
10 Contribution of CYP3A isoforms to dealkylation of PDE5 inhibitors: a comparison between sildenafil N-demethylation and tadalafil demethylenation. Biol Pharm Bull. 2015;38(1):58-65.
11 Pharmacotherapy of erectile dysfunction: focus on cardiovascular safety. Expert Opin Drug Saf. 2005 May;4(3):531-40. doi: 10.1517/14740338.4.3.531.
12 ClinicalTrials.gov (NCT01178073) A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)